The DOI matches its Crossref record; 42 of the 44 references it cites were found in a registry or an index.
Lipocalin 2-Dependent Inhibition of Mycobacterial Growth in Alveolar Epithelium
Open accessAbstract
Mycobacterium tuberculosis invades alveolar epithelial cells as well as macrophages. However, the role of alveolar epithelial cells in the host defense against M. tuberculosis remains unknown. In this study, we report that lipocalin 2 (Lcn2)-dependent inhibition of mycobacterial growth within epithelial cells is required for anti-mycobacterial innate immune responses. Lcn2 is secreted into the alveolar space by alveolar macrophages and epithelial cells during the early phase of respiratory mycobacterial infection. Lcn2 inhibits the in vitro growth of mycobacteria through sequestration of iron uptake. Lcn2-deficient mice are highly susceptible to intratracheal infection with M. tuberculosis. Histological analyses at the early phase of mycobacterial infection in Lcn2-deficient mice reveal increased numbers of mycobacteria in epithelial cell layers, but not in macrophages, in the lungs. Increased intracellular mycobacterial growth is observed in alveolar epithelial cells, but not in alveolar macrophages, from Lcn2-deficient mice. The inhibitory action of Lcn2 is blocked by the addition of endocytosis inhibitors, suggesting that internalization of Lcn2 into the epithelial cells is a prerequisite for the inhibition of intracellular mycobacterial growth. Taken together, these findings highlight a pivotal role for alveolar epithelial cells during mycobacterial infection, in which Lcn2 mediates anti-mycobacterial innate immune responses within the epithelial cells.
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“microbes require iron for growth, its presence may be limiting even at the scale of global CO2 fixation [1506-1509], its excess can in some circumstances [1510] correlate with infectivity or virulence (see above and e.g. [180,193,1493,1511-1531]), and its chelation in a form not available to bacteria offers a route to at least a bacteriostatic kind of antibiotic or to novel therapies based on the”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1533]
In the citing paper
“Importantly, Lcn2−/− mice are more susceptible to mycobacterial infections (214), which might be different from the iron-sequestrating role of Lcn2 (215) but rather due to its function as efficient chemoattractant for neutrophils to sites of infection (216–218).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [214]
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Metadata
- Authors
- Saiga, H., Nishimura, J., Kuwata, H., Okuyama, M., Matsumoto, S., Sato, S., Matsumoto, M., Akira, S., Yoshikai, Y., Honda, K., Yamamoto, M., & Takeda, K.
- Affiliations
- The University of Osaka (JP)
- Department of Molecular Genetics
- Osaka City University (JP)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Kyushu University (JP)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-12
- Volume
- 181
- Issue
- 12
- Pages
- 8521-8527
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1898659608
- Cited by
- 133
- References
- 44
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 10 · 2014: 11 · 2013: 13 · 2012: 19
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- neutrophil gelatinase-associated lipocalin, Mycobacterium tuberculosis, alveolar epithelial cells, innate immunity, iron sequestration, endocytosis, pulmonary tuberculosis, alveolar macrophages
- MeSH terms
- Lipocalin-2, Acute-Phase Proteins, Animals, Cell Line, Mice, Inbred C57BL, Mice, Transgenic, Mycobacterium bovis, Mycobacterium tuberculosis, Pulmonary Alveoli, Tuberculosis, Oncogene Proteins, Macrophages, Alveolar, Mice, Knockout, Respiratory Mucosa, Mice, Lipocalins
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